新血栓风险评估模型对恶性肿瘤患者静脉血栓形成的预测价值

doi:10.13481/j.1671-587X.20240524

Abstract

Abstract:

Objective To construct a new thrombus risk assessment model and evaluate its predictive ability for venous thromboembolism （VTE） in the patients with malignant tumors， and to provide the basis for the early predition of the malignant tumor patients with high risk for VTE. Methods A total of 128 untreated malignant tumor patients were included， of which 40 were diagnosed with VTE within 2 months of malignant tumor diagnosis and categorized as VTE group. A total of 88 patients who did not develop VTE were categorized as non-VTE group. The clinical risk factors and laboratory indicators of the patients in two groups were compared and analyzed； the types of thrombotic events of the patients were analyzed； the diagnostic values of thrombin-antithrombin-complex （TAT）， α2-plasmin inhibitor-plasmin complex（PIC）， D-dimer（D-dimer）， and fibrin degradation products（FDP） in malignant tumors complicated by VTE were assessed using receiver operating characteristic （ROC） curve analysis； Multivariate Logistic regression analysis was used to analyze the correlations of the clinical risk factors and biomarkers with the malignant tumors complicated with VTE. A new thrombus risk assessment model was constructed， consisting of TAT≥0.70 μg·L^-1， poor differentiation， and cardiovascular risk factors. The predictive probability of the model for malignant tumors complicated by VTE was evaluated based on the significance， goodness of fit， calibration curve， and C value of the model. The clinical application value of the new thrombus risk assessment model， COMPASS-CAT risk score （CRS）， and Khorana risk score （KRS） in assessing malignant tumor patients complicated by VTE was compared using the C value and decision curve analysis （DCA）. Results The plasma levels of TAT （P<0.001）， PIC （P<0.001）， D-dimer （P<0.05）， and FDP （P<0.01） of the patients in VTE group were higher than those in non-VTE group. Compared with the patients without cardiovascular risk factors， poor differentiation， and lymphatic metastasis， the malignant tumor patients with cardiovascular risk factors （P<0.001）， poor differentiation （P<0.001）， and lymphatic metastasis （P<0.05） were more likely to develop VTE. Most VTE events （65%） were isolated deep vein thromboembolism（DVT）. The ROC curve analysis showed that the area under the curve （AUC）， sensitivity， and specificity of TAT and PIC were higher than those of D-dimer and FDP. TAT≥0.70 μg·L^-1 （P<0.05）， poor differentiation （P<0.01）， and cardiovascular risk factors（P<0.01） were the independent risk factors for VTE in the malignant tumor patients. A new thrombus risk assessment model consisting of TAT≥0.70 μg·L^-1， poor differentiation， and cardiovascular risk factors was constructed. The new risk assessment model had a high goodness of fit （P=0.805） and good predictive ability during internal validation （χ²=75.266， P<0.001）. The ROC curve analysis results showed that the C values for the new thrombus risk prediction model， CRS， and KRS were 0.908， 0.676， and 0.541， respectively. The DCA curve analysis results showed that the new thrombus risk assessment model had a higher net benefit rate compared with CRS and KRS. Conclusion TAT and PIC have greater diagnostic efficiency than D-dimer in the early prediction of the malignant tumor patients with high-risk VTE. For the patients included in this study， the new thrombus risk assessment model， constructed from TAT≥0.70 μg·L^-1， poor differentiation， and cardiovascular risk factors， has superior diagnostic efficiency and clinical predictive value compared with CRS and KRS.

Key words: Malignant tumor, Venous thromboembolism, Biomarker, Risk factor, Risk assessment model

CLC Number:

R730.6

Honghong LI,Na YU,Minghao SHI,Ying SUN,Yao LI,Zhongjun SHEN,Xiaoyi LIU,Liyan ZHAO. Predictive value of new thrombotic risk assessment model for venous thromboembolism in patients with malignant tumors[J].Journal of Jilin University(Medicine Edition), 2024, 50(5): 1390-1399.

Figures/Tables 11

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References 34

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Variable	VTE group （n=40）	Non-VTE group （n=88）	t/F/U	P
Age（year）	61.73±10.41	58.91±13.40	1.168	0.245
Male（percentage of man）	16（40.00）	30（34.09）	0.417	0.518
BMI（kg·m^-2）	23.52±3.26	23.00±3.27	0.825	0.441
Hypofractionation[n（η/%)]	16（40.00）	10（11.36）	13.932	<0.001
Lymphatic metastasis[n（η/%)]	17（42.50）	21（23.86）	4.576	0.032
Distant metastasis[n（η/%)]	17（42.50）	32（36.36）	0.438	0.508
Cardiovascular risk factors[n（η/%)]	20（50.00）	13（14.77）	17.835	<0.001
Lung cancer[n（η/%)]	15（37.50）	32（36.36）	0.015	0.902
Colorectal cancer[n（η/%)]	13（32.50）	26（29.55）	0.113	0.736
Ovarian cancer[n（η/%)]	12（30.00）	30（34.09）	0.209	0.648
D-dimer（mg·L^-1)	1.17（0.46-2.63）	0.61（0.38-1.23）	-2.370	0.018
FDP（mg·L^-1)	5.40（3.20-8.60）	3.60（3.00-5.00）	-2.681	0.007
TAT（μg·L^-1)	0.93（0.80-1.05）	0.55（0.46-0.76）	-5.341	<0.001
PIC（μg·L^-1)	39.97（34.25-43.25）	21.74（12.90-35.67）	-5.742	<0.001

Tumor type	Treatment modality	n	VTE group	Non-VTE group	F	P
Lung cancer	Lobectomy	8	2（25.00）	6（75.00）	0.212	0.645
	Lobectomy+lymph node dissection	10	4（40.00）	6（60.00）	0.382	0.536
	Total lung resection+platinum-containing two-drug chemotherapy （single-cycle regimen）	29	9（31.03）	20（68.97）	0.027	0.869
Colorectal cancer	Local excision	27	9（33.33）	18（66.67）	0.000	1.000
	Miles+Xelox	5	2（40.00）	3（60.00）	0.115	0.735
	Miles+Folfox6	4	1（25.00）	3（75.00）	0.139	0.709
	Hartmann+Folfox6	3	1（33.33）	2（66.67）	0.000	1.000
Ovarian cancer	Tumor reduction surgery	20	4（20.00）	16（80.00）	1.375	0.241
	Tumor reduction surgery+paclitaxel（single-cycle regimen）+carboplatin（single-cycle regimen）	22	8（36.36）	14（63.64）	1.375	0.241

VTE site	Incidence
DVT alone	26（65.0）
PE alone	8（20.0）
DVT and PE	7（17.5）
DVT and ULVT	3（7.5）
ULVT alone	1（2.5）

Variable	Cut-off value	Sensitivity（η/%）	Specificity（η/%）	Youden index	AUC	95%CI of AUC
TAT	0.695	75.0	90.0	0.650	0.821	0.735-0.906
PIC	31.257	68.2	85.0	0.532	0.817	0.745-0.890
D-dimer	1.050	57.5	69.3	0.268	0.630	0.525-0.735
FDP	5.150	57.5	72.7	0.302	0.634	0.529-0.740

Variable	Tolerance	VIF
TAT≥0.70 μg·L^-1	0.229	4.365
PIC≥31.26 μg·L^-1	0.221	4.520
D-dimer≥1.05 mg·L^-1	0.037	26.923^*
FDP≥5.15 mg·L^-1	0.037	27.027^*
Hypofractionation	0.929	1.076
Lymphatic metastasis	0.938	1.066
Cardiovascular risk factors	0.969	1.032

Predictive value of new thrombotic risk assessment model for venous thromboembolism in patients with malignant tumors

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Variable	β	SE	Wald	OR	95%CI	P
TAT≥0.70 μg·L^-1	3.062	1.435	4.556	21.387	1.285-356.097	0.033
PIC≥31.26 μg·L^-1	1.887	1.473	1.642	6.601	0.368-118.352	0.200
Hypofractionation	3.751	1.232	9.268	42.548	3.804-475.968	0.002
Lymphatic metastasis	0.661	0.597	1.226	1.938	0.601-6.247	0.268
Cardiovascular risk factors	1.912	0.653	8.570	6.770	1.882-24.357	0.003

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